Interpretation and bias in case-crossover studies

The case-crossover design is an innovative epidemiologic technique with distinct strengths and limitations. We review the fundamental logic of this self-matching non-randomized design and direct attention to 15 concerns related to the available data, unavailable data, analytic technique, quantitative statistics, and etiologic model. Implications for each concern are discussed in the context of a recent report on whether cellular telephone calls are associated with an increased risk of a motor vehicle collision. We suggest that an understanding of the case-crossover design may help investigators explore selected questions in behavioral medical research.